Use of the distrontium salt of the acid 2-[n,n-di(carboxymethyl)amino]-3-cyano-4-carboxy- methyl-thiophene-5-carboxylate for the production of medicaments for the treatment of gastro-duodenal pain

ABSTRACT

The present invention relates to the use of the distrontium salt of 2-[N,N-di(carboxymethyl)amino]-3-cyano-4-carboxymethyl-thiophene-5-carboxylic acid in obtaining medicaments intended for the treatment of gastro-duodenal pain.

The present invention relates to use of the distrontium salt of2-[N,N-di(carboxymethyl)amino]-3-cyano-4-carboxymethyl-thiophene-5-carboxylicacid in obtaining medicaments intended for the treatment ofgastro-duodenal pain.

The distrontium salt of2-[N,N-di(carboxymethyl)amino]-3-cyano-4-carboxymethyl-thiophene-5-carboxylicacid has been described in patent specification EP 0 415 850. Itsanti-osteoporotic properties allow it to be used in bone diseases suchas osteoporosis. It may also be used in the treatment of cutaneous andvascular ageing, liver disorders and dental disorders.

The distrontium salt of2-[N,N-di(carboxymethyl)amino]-3-cyano-4-carboxymethyl-thiophene-5-carboxylicacid moreover has anti-arthrosic properties making it useful in thetreatment of arthrosis as described in patent specification EP 0 813869.

The Applicant has now discovered that the distrontium salt of2-[N,N-di(carboxymethyl)amino]-3-cyano-4-carboxymethyl-thiophene-5-carboxylicacid of formula (I) and hydrates thereof have gastro-protectiveproperties allowing their use in obtaining medicaments intended for thetreatment of gastro-duodenal pain:

Indeed, it has been shown in a clinical study that the compound offormula (I), which is also referred to as strontium ranelate, was ableto bring about a significant improvement in gastric pain.

This result is all the more surprising in that, during an in vivo studycarried out with a different strontium salt (strontium chloride), it wasobserved that strontium chloride very rapidly caused superficialhaemorrhagic lesions in the animals treated.

The person skilled in the art would doubtless not have imagined that adifferent strontium salt, in this case strontium ranelate, would allowthe reverse effect to be obtained.

These entirely surprising results accordingly make it possible toconsider using strontium ranelate and hydrates thereof in obtainingpharmaceutical compositions for use in the treatment of gastro-duodenalpain and especially gastritis and duodenitis and any inflammation of themucosa of the stomach whether acute or chronic.

Gastritis and duodenitis correspond to irritative states of thedigestive mucosa which are accompanied by daily abdominal pain in rhythmwith meals. They are aggravated by different types of food or alcoholicdrinks. They may precede the onset of ulcers. They justify theadministration of various treatments in order to protect the mucosa orto reduce acid secretion.

The pharmaceutical compositions will be presented in forms suitable foradministration by the oral, parenteral, transcutaneous, nasal, rectal orperlingual route, especially in the form of injectable preparations,tablets, sublingual tablets, glossettes, gelatin capsules, capsules,lozenges, suppositories, creams, ointments, dermal gels, etc.

In addition to strontium ranelate or, where appropriate, hydratesthereof, the pharmaceutical compositions according to the inventioncomprise one or more excipients or vehicles selected from diluents,lubricants, binders, disintegrating agents, absorbents, colourants,sweeteners, etc.

By way of non-limiting example, there may be mentioned:

-   -   as diluents: lactose, dextrose, sucrose, mannitol, sorbitol,        cellulose, glycerol,    -   as lubricants: silica, talc, stearic acid and its magnesium and        calcium salts, polyethylene glycol,    -   as binders: aluminium silicate, magnesium silicate, starch,        gelatin, tragacanth, methylcellulose, sodium        carboxymethylcellulose and polyvinylpyrrolidone,    -   as disintegrating agents: agar, alginic acid and its sodium        salt, effervescent mixtures.

The useful dosage varies according to the sex, age and weight of thepatient, the administration route, the nature of the disorder and anyassociated treatments, and ranges from 25 mg to 6 g of strontiumranelate per 24 hours, for example from 100 mg to 4 g of compound per 24hours.

The daily dose of strontium ranelate will preferably be 2 g per day.

Clinical Study:

This study was carried out in 1649 patients. 719 were treated withstrontium ranelate, 723 were treated with a placebo. The duration oftreatment was 1101±321 days. The dose of strontium ranelate administeredwas 2 g/day.

After treatment it was observed that gastric pain was significantlyreduced in the group of patients treated with strontium ranelate (atleast 30%) compared to the group of patients treated with placebo.

1-3. (canceled)
 4. A method for treating a living animal body, includinga human, afflicted with a condition associated with gastro-duodenalpain, comprising the step of administering to the living animal body,including a human, an amount of the distrontium salt of2-[N,N-di(carboxymethyl)amino]-3-cyano-4-carboxymethyl-thiophene-5-carboxylicacid or hydrates thereof which is effective for alleviation of thecondition.
 5. The method of claim 4, wherein the condition associatedwith gastro-duodenal pain is gastritis.
 6. The method of claim 4,wherein the condition associated with gastro-duodenal pain isduodenitis.